Statewide gathering goes viral

ASU, UA team up for conference on virology

November 14, 2017

Arizona State University and the University of Arizona — infamous rivals on the playing field — joined forces for a special joint conference on virology. The first-of-its-kind event took place at the Biodesign Institute at ASU on Friday, Nov. 3 and presented a broad range of research concerning one of the more enigmatic entities in the biological world.

The gathering was co-hosted by Grant McFadden, director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy (CIVV) and Felicia Goodrum of the Bio5 Institute at UA. The get-together marked the first opportunity for virologists from across the state to present up-to-the-minute research, share ideas and plan future collaborative projects. Participants in this year's ASU-UA joint symposium on virology. Pictured (front row right) the co-organizers: Felicia Goodrum, of UA and BIO5, and Grant McFadden, director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy. Download Full Image

McFadden opened the interactive all-day symposium, outlining the menu for the day’s lectures. Each of the eight speakers presented a 20-minute talk, followed by a 10-minute Q&A session. The event featured researchers from ASU and UA, with the exception of the opening plenary lecture. As McFadden explained, “fortunately, it so happens that an eminent external virologist — Susan Weiss — is visiting us.”

Professor Weiss was then introduced by her friend, colleague and fellow coronavirus specialist Brenda Hogue, a virologist in Biodesign’s CIVV. In her introduction, Hogue observed the impressive rise in virology research in Arizona, since her arrival at ASU in 2002. She noted Weiss’ contributions to the study of coronaviruses, viral pathogenesis and neurovirology.

Weiss is a professor of microbiology at the University of Pennsylvania, associate dean for postdoctoral research training, and director in the Office of Biomedical Postdoctoral Programs. Her lecture focused on a specific pathway of critical importance for the virus-host interaction characteristic of coronavirus infection. (The name of this RNA virus comes from the halo-like appearance of a coronavirus particle or virion, when seen under an electron microscope.)

Weiss’ lab studies the betacoronavirus MHV in order to investigate acute viral encephalitis, demyelinating diseases such as multiple sclerosis and virus-induced hepatitis.

As Weiss noted, coronaviruses had been largely ignored in the field of virology until November 2002, when a now-infamous member of the coronaviridae family burst on the scene in China, producing an epidemic of Severe Acute Respiratory Syndrome or SARS. The disease resulted in the deaths of 774 people in 37 countries, with the majority of fatalities occurring in China.

Coronaviruses are primarily respiratory pathogens, with members like OC43 and 229E producing common colds, while SARS and the later-identified MERS (for Middle East Respiratory Syndrome) lead to serious, life-threatening illness. The SARS and MERS coronaviruses are newly emerged viruses with fatality rates of ~15 percent and 35 percent, respectively. The MERS virus continues to cause infections and is a global concern.

The talk focused on mechanisms used by coronaviruses to outwit host defenses. A key part of the process involves the action of virus-induced phosphodiesterase that acts to disable a key antiviral pathway known as OAS-RNase L.

Next on the program, Koenraad Van Doorslaer of UA and BIO5 turned the discussion to another human pathogen, papillomavirus — more specifically, the Alpha papillomavirus, which is believed to be responsible for virtually all cases of cervical cancer. Curiously, different strains of Alpha papillomavirus produce widely varying levels of pathogenicity, from benign to extremely carcinogenic.

Van Doorslaer’s investigations focus on understanding of the underlying molecular mechanisms differentiating oncogenic from nononcogenic viral forms, by applying functional screenings of viruses with an eye toward viral epidemiology and evolutionary history. He emphasizes that the emerging picture of viral oncogenicity is more complex than originally appreciated in the field.

Herpes viruses were the subject of Ian Hogue’s talk. Hogue, a recent addition to the faculty of Biodesign’s CIVV, studies neurovirology, the molecular and cell biology of viruses in the nervous system. Specifically, Hogue’s laboratory uses specialized live-cell fluorescence microscopy methods, cryo electron microscopy structural biology methods, and primary neuron cell culture methods to study how alpha herpes viruses interact with the molecular and cell biology of neurons.

Herpes viruses constitute a highly diverse family known to affect mammals, birds, reptiles, amphibians, fish, and even oysters, co-evolving with their natural hosts for tens or hundreds of millions of years. The viruses in the alpha herpesvirus sub-family including human Herpes Simplex Virus 1 & 2 (HSV-1 & -2) and Varicella-Zoster Virus (VZV), infect neurons and are among the very few viruses that have evolved to make their living in the mammalian nervous system. The virus can enter a prolonged state of dormancy. Periodically, the HSV-1 virus may be reactivated to resume its normal cycle of gene expression, generating new viruses that travel back along axons to the periphery.

Hogue’s lecture described the means by which a particular alpha herpesvirus — PRV (for pseudorabies virus) — might exit from infected cells and spread along circuits of synaptically connected neurons. The research unexpectedly showed that transneuronal virus spread is not correlated with action potential firing—a finding of great importance in understanding alpha herpesviruses’ ability to spread through the nervous system.

Sam Campos, an assistant professor of immunology from the University of Arizona's Cancer Center described high-risk human papillomaviruses (HPVs), the most prevalent sexually transmitted infections, responsible for 5 percent of cancers worldwide. These oncogenic viruses establish persistent infections in the mucosal epithelium. Campos' described HPV’s unique entry pathway, which allows the virus to evade important immune pathways.

His work is aimed at deepening the understanding of fundamental HPV biology, particularly, the viral mechanisms of immune evasion and persistence.

Bert Jacobs, Biodesign virologist and director of ASU’s School of Life Sciences, shared his knowledge of another very large family of important viruses — the poxviruses. Jacobs presented recent research results bearing on vaccinia (VACV), a double-stranded DNA poxvirus that was famously used in a vaccine to successfully eradicate smallpox and has subsequently been explored by Jacobs and others as possible vector for immunization against other viruses.

Jacobs’ talk outlined the mechanisms by which poxvirus inhibits necrotic cell death using an innate immune evasion protein, E3. Virus-induced cell death — known as necroptosis — is an important innate defense mechanism used by vertebrates to safeguard cells against infections by poxviruses, as well as herpesviruses and the influenza A virus.

The new research presents a plausible mechanism for the inhibition of necroptosis by VACV, resolving the longstanding issue of evasion protein E3’s role in inhibiting the host interferon system and paving the way for improved diagnostics and therapeutics.

The next talk moved from viral infection to parasitic infection. Anita Koshy is an assistant professor in the Department of Neurology, as well as in the Department of Immunobiology at UA and a researcher in BIO5. Her research focuses on how the common parasite, Toxoplasma gondii persists in the brain, using a mouse model of parasitic infection. Neurons are the primary target cell for Toxoplasma gondii, a parasite believed to have already infected one third of the world’s population. 

The parasite acts to alter the immune environment in the brains of those it infects, thereby carving out a hospitable environment. The work points to possible methods to control the immune environment in the brain and intervene in other diseases where inflammation of the brain may be present.

Paul Boehmer, interim associate dean for research, chair and professor in the UA College of Medicine, Phoenix, next spoke about genome maintenance in another alpha herpes virus: HSV-1, a large, double-stranded DNA virus that is neurotropic, establishing latent, life-long infections within sensory neurons. In the course of its complex life cycle, HSV-1 executes a complex chain of events aimed at optimizing replication. The talk focused on the means by which the virus maintains its genome and the emergence of the virus from neuronal latency.

The symposium concluded with a presentation by John Purdy, from UA’s College of Medicine, immunobiology department and BIO5. Purdy turned attention to another virus causing lifelong infections in over 60 percent of the world’s population, the Human Cytomegalovirus (HCMV), which is a ß–herpesvirus.   

Often, carriers are asymptomatic, but some — particularly those with weakened immune systems — may be vulnerable to serious health effects. It can also affect babies infected with the virus before birth. (HCMV is a major source of birth defects, an opportunistic infection in HIV/AIDS cases and a potential life-threatening complication in transplant patients.)

Purdy outlined the process by which the HCMV pathogen is able to rewire the host cell’s metabolism, turning it to the benefit of the virus. The research has implications for the study of other host-viral interactions.

Following the symposium, McFadden shared the hope that the event will become a growing part of the scientific landscape in Arizona, with meetings hosted again at Biodesign as well as in Downtown Phoenix, Tucson, Flagstaff and beyond.

Richard Harth

Science writer, Biodesign Institute at ASU


ASU student inspires others to rethink immigration

Project to find students' own immigration story in their family tree results in website, exhibit launching Nov. 16

November 14, 2017

Although the majority of Americans would not be here if it weren’t for immigration, there are many today who might distance themselves from their family’s immigration history.

Judith Perera, a PhD candidate studying the history of immigrant detention in the U.S. in Arizona State University's School of Historical, Philosophical and Religious Studies, realized the way immigration is taught and talked about does not reflect the process and reality of the immigrant experience. She has created a project for her students to break down their ideas of immigration by applying their own family to the narrative. Perera's HST 325 class Download Full Image

“If I can get them to place themselves and their families into the narrative, then perhaps they can see themselves in the history and it can be more relevant to them,” said Perera. “In this process I know other people don’t think about how they are descendants from immigrants, so they don’t really think about that process. So how does an immigrant instructor get someone on the same page? How do you get students engaged?”

Her answer came after she visited the Southwest Oral History Conference in April. She was impressed by the use of oral history in classrooms as well as in the community and decided to apply it to her own teachings.

“I think traditional history courses are lecture-based, exam-based, paper-based, and my courses don’t really do that,” said Perera. “You are teaching to dramatically different students. They have a lot of information accessible at their fingertips with their phones so you don’t necessarily need to be as lecture-based. Rather, let's think about things, let's talk about things.”

The topic of immigration is important to Perera as she is an immigrant herself. She immigrated to the U.S. from Sri Lanka when she was 11 years old. She said her own experience of coming to America is one that many of her students have trouble relating to, so she has made it her priority to ask them to look to history for their own tale.

“To me, being an immigrant myself, it’s something I kind of think about on a daily basis,” said Perera. “So while at the same time I’m researching, it’s not like I can go home and say, ‘OK, research over. I’m going to do my own life,’ you know? You wake up and you eat, sleep, breathe it.”

Perera decided to have her students take on a project called “Our Stories,” in which students found their immigration story within their families. They traced back to when their families came to America and have put together posters for an exhibit in Hayden Library.

“If I can get every student to acknowledge their own immigrant story, can others in the public do the same?” asked Perera. “What impact might that have in changing the way we approach immigration or think about immigration? Just showing more compassion, kindness, empathy towards people.”

The posters will be displayed in the library from Nov. 16 until Dec. 8. There is also a website dedicated to the project, and there will be a documentary premiering on Dec. 1 at the Marston Exploration Theater on the ASU Tempe campus.

“The students have been so incredible,” said Perera. “The students are going above and beyond what they have to do, and they have taken so much time to build this. It’s remarkable.”

Rachel Bunning

Communications program coordinator, School of Historical, Philosophical and Religious Studies